StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

BMC Bioinformatics

Methodology Article

Raul Andino¹  Carol L Ecale Zhou²  Dorothy M Lang²  Adam T Zemla²  Tanya Kostova³ 

[1] Department of Microbiology and Immunology, University of California, 94143, San Francisco, CA, USA;Global Security Computing Applications Division, Lawrence Livermore National Laboratory, 94550, Livermore, CA, USA;National Science Foundation, 22230, Arlington, VA, USA;

关键词: Protein Data Bank;    Structure Fragment;    Distance Cutoff;    Sequence Variability;    Query Structure;   

DOI  :  10.1186/1471-2105-12-226

 received in 2010-12-15, accepted in 2011-06-02,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundMost of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures.ResultsHere we present StralSV (str ucture-al ignment s equence v ariability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses.ConclusionsStralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.

【 授权许可】

CC BY   
© Zemla et al; licensee BioMed Central Ltd. 2011